Bismuth-based Quadruple Therapy Research Articles

Bismuth-Based Quadruple Therapy as First-Line Treatment for Clarithromycin-resistant Helicobacter pylori Infection: A Prospective Randomized Comparison of 7- and 14-Day Treatment Regimens.

: Bismuth-based quadruple therapy (BQT) is a treatment option for clarithromycin-resistant Helicobacter pylori (HP) infection. The aim of this study was to compare the efficacy of 7-day BQT with that of 14-day BQT as first-line treatment for clarithromycin-resistant HP infection. : A total of 162 treatment-naïve patients with peptic ulcer disease and clarithromycin-resistant HP infection confirmed by real-time polymerase chain reaction (RT-PCR) were enrolled. The enrolled patients were prospectively randomized to receive BQT for either 7 or 14 days of treatment. Eradication of HP infection was assessed using a 13C-urea breath test. Eradication and adverse event rates of the two groups were assessed. : The overall eradication rates in the intention-to-treat (ITT) and per-protocol (PP) analyses were 83.0% (95% confidence interval [CI], 77.2% to 88.9%; 132/159) and 89.8% (95% CI, 84.9% to 94.7%; 132/147), respectively. The eradication rates in the ITT analysis were 79.0% (64/81) in the 7-day group and 87.2% (68/78) in the 14-day group (p=0.170). The eradication rates in the PP analysis were 86.5% (64/74) in the 7-day group and 93.2% (68/73) in the 14-day group (p=0.182). Clinically significant adverse events occurred in 18.2% of patients. There was no statistically significant difference in the rates of individual or all adverse events between the two groups. : Both 7-day and 14-day BQT were effective and safe as first-line therapy for HP infections identified as resistant to clarithromycin by RT-PCR. For clarithromycin-resistant HP infections, 7-day BQT may be sufficient as first-line therapy.

An all-in-one therapeutic platform for the treatment of resistant Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection is a major cause of gastric diseases. Currently, bismuth-based quadruple therapy is widely adopted for eradicating H. pylori infection. However, this first-line strategy faces several challenges such as drug resistance, intestinal dysbacteriosis, and patients’ poor compliance. To overcome these problems, an all-in-one therapeutic platform (CLA-Bi-ZnO2@Lipo) that composed of liposomes loading clarithromycin (CLA), Bi, and ZnO2 hybrid nanoparticles was developed for eradicating multidrug-resistant (MDR) H. pylori. The in vitro and in vivo results showed that CLA-Bi-ZnO2@Lipo could target the infection-induced inflammatory mucosa through liposome mediated nanoparticle-tissue surface charge interaction and quickly respond to the gastric acid environment to release CLA, Bi3+, Zn2+, and H2O2. By oral administration per day, the acid triggered decomposition of CLA-Bi-ZnO2@Lipo could significantly increase intragastric pH to 6 within 30 min; The released CLA, Zn2+, and H2O2 further exerted synergistical anti-bacterial effects in which a ∼2 order higher efficacy in reducing MDR H. pylori burden was achieved in comparison with standard quadruple therapy (p < 0.05); The released Zn2+ and Bi3+ could also alleviate mucosal inflammation. Most importantly, the CLA-Bi-ZnO2@Lipo exhibited superior biosafety and nearly no side effects on intestinal flora. Overall, this study developed a highly integrated and safe anti-MDR H. pylori agent which had great potential to be used as an alternative treatment for MDR H. pylori eradication.

Meta-analysis of Helicobacter pylori eradication therapy using vonoprazan as an acid suppressor compared with bismuth quadruple therapy.

Vonoprazan, a novel acid suppressant, has recently emerged as a regimen for eradicating Helicobacter pylori. However, uncertainties exist about the effectiveness and safety of VPZ-based regimens compared with those of bismuth-based quadruple therapy in eradicating H. pylori. The present meta-analysis was performed to compare the effectiveness and safety of vonoprazan-based regimens with those of bismuth quadruple therapy in eradicating H. pylori. All randomized controlled trials and non-randomized controlled trials comparing the vonoprazan-based therapy with the bismuth quadruple therapy were included in this meta-analysis. Information was also extracted by two evaluators, and if heterogeneity existed, a random-effects model was used to calculate the combined relative ratio and 95% confidence interval; otherwise, a fixed-effects model was used. And subgroup analyses were performed to explore the sources of heterogeneity. A total of 10 studies, comprising 2587 patients were included in the meta-analysis. The results showed that the combined eradication rate of patients treated with the vonoprazan-based regimen was significantly higher than that of patients treated with bismuth quadruple therapy, in both intention-to-treat and per-protocol analyses, and the differences were statistically significant. Among the intention-to-treat analyses results: (90.28% vs. 83.64% [odds ratio (OR) = 1.85, 95% confidence interval (CI) (1.27, 2.70), p = 0.001]); in the per-protocol analyses: (94.80% vs. 89.88%, [OR = 2.25, 95% CI (1.37, 3.69), p = 0.001]). The occurrence of adverse events was significantly lower in patients treated with vonoprazan-based regimens than in those treated with bismuth quadruple therapy, (14.50% vs. 25.89%, [OR = 0.49, 95% CI (0.32, 0.75), p = 0.001]). For eradicating H. pylori, vonoprazan-based regimens are remarkably advantageous over bismuth quadruple therapy. Furthermore, vonoprazan-based regimens exhibit a lower rate of adverse events than bismuth quadruple therapy.

Influence of Helicobacter pylori Infection and Eradication on Small Intestinal Bacterial Overgrowth and Abdominal Symptoms.

The relationship between Helicobacter pylori (H. pylori) infection and small intestinal bacterial overgrowth (SIBO) has attracted attention recently. To analyze the influence of H. pylori infection and eradication on SIBO, IMO, and abdominal symptoms. Patients with gastrointestinal symptoms were tested for 13C urea breath test and if positive, treated with bismuth-based quadruple therapy. Lactulose hydrogen methane breath test (HMBT) was performed and symptoms were assessed using gastrointestinal symptom rating scale (GSRS) before and 6weeks after eradication. Of the 102 subjects, 53 were H. pylori positive. The prevalence of SIBO and IMO were higher in patients with H. pylori infection than in those without infection (49.1% vs 24.5%, P = 0.019 for SIBO; 24.5% vs 8.2%, P = 0.027 for IMO). GSRS scores were similar between H. pylori-infected and uninfected patients (2 (IQR: 1;3) vs 2 (IQR: 1;2), P = 0.211). Patients with SIBO or IMO presented higher GSRS scores than patients with both SIBO and IMO negative (2 (IQR: 2;3), 2 (IQR: 2;3) vs 2 (IQR: 1;2), P = 0.011, 0.001, respectively). For the 50 patients who successfully eradicated H. pylori, the response rates for SIBO and IMO were 66.7% and 76.9%, respectively. GSRS scores also significantly decreased (2 (IQR: 1;3) to 0 (IQR: 0;1), P < 0.001) after eradication. Helicobacter pylori infection was associated with higher prevalence of SIBO and IMO, both of which led to more pronounced abdominal symptoms. H. pylori eradication also achieved therapeutic effects on SIBO and IMO, accompanied by relief of abdominal symptoms.

Success of Helicobacter pylori Guideline-based Treatment of Newly Diagnosed and Previously Treated Patients During 2007–2021 in Edmonton, Alberta

Abstract Background Updated 2016 Helicobacter pylori consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC) or bismuth-based quadruple therapy (PPI-bismuth-metronidazole-tetracycline, PBMT)) as first line, PBMT or PPI-amoxicillin-levofloxacin (PAL) as second or third line, and PPI-amoxicillin-rifabutin (PAR) as fourth line for 10 days. Objectives This was a retrospective cohort study to describe and compare the efficacy of anti-Helicobacter treatment regimens over the periods 2007–2015 and 2016–2021 as well as antibiotic resistance. Methods A modified intention-to-treat (mITT) analysis was used to analyze the success rate of therapies. mITT includes all patients who were prescribed H. pylori treatment and had at least one follow-up test-of-cure. This included patients who could not complete treatment or were non-adherent with treatment. Risk factors for treatment failures were analyzed by univariate and multivariate logistic regression. Resistance testing was done in a small subset of patients. Results H. pylori-positive patients who received treatment in Edmonton, Alberta were included in a mITT analysis: 334/387(86%) from 2007 to 2015 and 193/199 (97%) from 2016 to 2021. During 2016–2021, 78% (150/193) of patients underwent cumulative guideline-based treatment with a successful cure in 80% (120/150) of patients. In those who were newly diagnosed, the cure rate was 88% (52/59) versus those with previous treatment failure 75% (68/91) (P &amp;lt; 0.05, risk difference [RD] 14%, 95% confidence interval [CI] 1.7–26.3%). The most effective first-line regimens were PAMC for 14 days (87% [45/52]) in 2016–2021 and sequential therapy in 2007–2015 (83% [66/80]) (P = 0.535, RD 4%, 95% CI −8.5–16.5%). When other treatments failed, success with PAR was 50% (2/4) from 2007 to 2015 and 57% (21/37) from 2016 to 2021. Recent (2016–2021) resistance rates to clarithromycin and metronidazole are high at 78% (50/64) and 56% (29/52), respectively. From 2007 to 2015, clarithromycin and metronidazole resistance rates were 80% (36/45) and 83% (38/46), respectively. Levofloxacin resistance increased significantly from 2007–2015 to 2016–2021 (28% [13/46] to 61% [35/57], P &amp;lt; 0.05, RD 33%, 95% CI 11.6–54.4%). Conclusions Algorithmic treatment with PAMC first line followed by PBMT, PAL, and PAR cures H. pylori in 88% of newly diagnosed patients. PAR therapy shows suboptimal cure rates (50–57% success) but can be considered as third instead of fourth line given increasing levofloxacin resistance rates. Antibiotic resistance in H. pylori is common to clarithromycin, metronidazole, and levofloxacin and frequently accounts for treatment failures.

Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. ChiCTR2300070100.

Real-world practice of Helicobacter pylori management: A survey among physicians in Southeast Asia.

Multidrug-resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real-world practice in H. pylori management. Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide. There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p < 0.001). Choosing inappropriate regimens containing antibiotics with high resistance rates is not uncommon in Southeast Asia, especially among non-GI physicians. In countries with high clarithromycin resistance, the PBMT regimen is underutilized.

Efficacy of 7-day Tailored Therapy for Helicobacter pylori Eradication based on Clarithromycin Resistance.

Increasing resistance to clarithromycin (CAM) of Helicobacter pylori (H. pylori) is one of the main causes of recent decrease in eradication rate of standard triple therapy. The aim of this study was to evaluate the usefulness of 7-day tailored therapy based on the existence of CAM resistance. From January 2017 to May 2022, a total of 481 consecutive patients with H. pylori infection were recruited in Daegu Catholic University Medical Center. Treatment regimen was selected based on the result of CAM resistance test. Patients with CAM resistance (R group) were treated with bismuth-based quadruple therapy for 7 days. Patients without CAM resistance (S group) were treated with standard triple therapy for 7 days. The overall H. pylori eradication rate was 89.4% (379 of 424) by per-protocol (PP) analysis. Patients with CAM resistance mutation included 166 patients (34.5%). The eradication rates of each group were 88.8% (135 of 152) and 89.7% (244 of 272) by PP analysis, for R and S group respectively. By intention-to-treat (ITT) analysis, the eradication rates were 81.3% (135 of 166) and 77.5% (244 of 315) for R and S group. CAM resistance was identified with a dual-priming oligonucleotide-based multiplex PCR. In spite of this high CAM resistance (34.5%), the eradication rate of 7-day tailored therapy based on the existence of CAM resistance was 89.4%. The 7-day tailored therapy based on CAM resistance could be an acceptable treatment selection strategy for H. pylori eradication.

Comparison of the efficacies of triple, quadruple and sequential antibiotic therapy in eradicating Helicobacter pylori infection: A randomized controlled trial.

There is regional variation in the eradication rates of Helicobacter pylori (H. pylori) regimens depending on the local antibiotic resistance patterns. The aim of this study was to compare the efficacies of triple, quadruple and sequential antibiotic therapy in eradicating H. pylori infection. A total of 296 H. pylori-positive patients were randomized to receive one of the three regimens (triple, quadruple or sequential antibiotic therapy) and eradication rate was assessed by H. pylori stool antigen test. The eradication rates of standard triple therapy, sequential therapy and quadruple therapy were 93%, 92.9% and 96.4%, respectively (p = 0.57). Fourteen days of standard triple therapy, 14 days of bismuth-based quadruple therapy and 10 days of sequential therapy are equally efficacious in eradicating H. pylori and all regimens have optimum H. pylori eradication rates. ClinicalTrials.gov Identifier: CTRI/2020/04/024929.

Egg yolk antibody combined with bismuth-based quadruple therapy in Helicobacter pylori infection rescue treatment: a single-center, randomized, controlled study.

The increasing antibiotic resistance is the main issue causing Helicobacter pylori (H. pylori) eradication failure. As a nutritional supplement, Egg Yolk Antibody (Ig Y) provides a new approach for H. pylori infection rescue therapy. In this randomized, controlled study, 100 H. pylori-positive patients with previous H. pylori eradication treatment were included. All individuals received standard bismuth-containing quadruple therapy twice daily (5 mg ilaprazole, 100 mg doxycycline, 500 mg clarithromycin or 1 g amoxicillin or 100 mg furazolidone, and 220 mg colloidal bismuth tartrate) for 14 days and were randomized to receive either twice daily 7 g Ig Y-H. pylori treatment (study group) or not (control group). 4 weeks after the end of treatment, urea breath tests were used to assess the H. pylori eradication rate. All participants scored by the Global Overall Symptom scale (GOS) and recorded adverse events during the trial. The H. pylori eradication rates were 84.0% (95% CI 73.5-94.5%) vs. 80.0% (95% CI 68.5-91.5%) in the study and control groups at intention-to-treat (ITT) analysis and 85.7% (95% CI 75.6-95.9%) vs. 80.0% (95% CI 68.5-91.5%) at per-protocol (PP) analysis, respectively. The number of over 80% symptom relief after treatment in the two groups was 27 (60%) and 12 (29.2%) (p < 0.05), and the incidences of adverse events were 4 (8%) and 6 (12%), respectively. Both groups achieved satisfactory eradication efficiency in H. pylori rescue therapy and Ig Y-H. pylori effectively alleviates the symptoms with good compliance and fewer adverse effects.

Current trends in &lt;i&gt;Helicobacter pylori&lt;/i&gt; eradication therapy

According to the Maastricht VI consensus, the triple therapy (PPI + clarithromycin + amoxicillin) and bismuth-based quadruple therapy (PPI + bismuth + tetracycline + metronidazole) are considered and may be proscribed empirically as first-line regimens in the regions with low clarithromycin resistance rates (&lt;15%). In the regions with high clarithromycin resistance rates (&gt; 15%), as well as in the regions with unknown resistance to this antibacterial agent, it is recommended to use classical quadruple therapy with bismuth drugs as the main choice and quadruple therapy without bismuth drugs (“simultaneous” or “concomitant”) as an alternative. The second-line regimens of empiric choice (when antimicrobial susceptibility testing is not available) include fluoroquinolone-based quadruple therapy (PPI + levofloxacin + amoxicillin + bismuth) or fluoroquinolone-based triple therapy (PPI + levofloxacin + amoxicillin) and bismuth-based quadruple therapy. The Maastricht VI consensus regulates the use of rifabutin-based triple therapy (PPI + amoxicillin + rifabutin) as a “rescue” therapy, if the above ET schemes are ineffective and there is no possibility to conduct an antimicrobial susceptibility test. In its latest clinical guidelines, the Russian Gastroenterological Association (RGA) recommends with a view to achieving maximum treatment efficiency during classic triple ET and levelling the risk of further progression of clarithromycin resistance in Russia to take additional measures to increase its effectiveness (detailed instruction of a patient and control over strict adherence to the prescribed regimen, prolonging the course up to 14 days; prescribing PPI at increased dose twice a day; the latest generation PPIs (rabeprazole and esomeprazole); adding bismuth tripotassium dicitrate (240 mg 2 times a day) to the standard triple therapy; adding cytoprotector rebamipide (100 mg 3 times a day) to the standard triple therapy; adding a probiotic with proven efficacy to the standard triple therapy within controlled studies).

İKİNCİ BASAMAK DEVLET HASTANESİNDE İKİ FARKLI HELICOBACTER PYLORI TEDAVİ REJİMİNİN ETKİNLİĞİNİN DEĞERLENDİRİLMESİ.

Objective: Helicobacter pylori (H. pylori) is a bacterium that infects more than half of the world's population and is defined as a class 1 carcinogen by the World Health Organization. The aim of this study is to compare the efficacy of treatments in patients with H. pylori positivity who were treated with a modified sequential treatment regimen containing levofloxacin or a bismuth-based quadruple treatment regimen in a secondary state hospital. Method: This study includes retrospective analysis of 167 patients who received and tolerated H. pylori eradication therapy between April 2021 and April 2022. The patients included in the study were divided into two groups according to the treatment regimen they received. Patients given a modified sequential treatment regimen containing levofloxacin (amoxicillin 1 g 2x1, pantoprazole 40 mg 2x1 for 7 days, followed by pantoprazole 40 mg 2x1 for 7 days, metronidazole 500 mg 3x1, levofloxacin 500 mg 1x1) Group 1 and the patients who were given bismuth-based quadruple therapy (14 days pantoprazole 40 mg 2x1, bismuth subsalicylate 262 mg 2x2, metronidazole 500 mg 3x1 and tetracycline 500 mg 4x1) were determined as Group 2.&#x0D; Results: A total of 14 patients (one in group 1 and 13 in group 2) could not tolerate H.pylori treatment, and eradication was achieved in 83 (90.2%) in group 1 and 70 (93.3%) in group 2 of 167 patients who completed the treatment. There was no statistically significant difference in eradication success rates in both treatment protocols (p=.470). There was no significant difference between the treatment groups in terms of age, gender, indications for endoscopy, endoscopic diagnoses, pathological findings, and eradication indications.&#x0D; Conclusion: Considering the eradication success rates found in our study, it supports that the modified sequential treatment regimen containing levofloxacin may be an alternative to bismuth-based treatment in the first-line treatment in our country, or a second-line treatment in patients who cannot tolerate bismuth-based treatment. However, further studies on modified sequential therapy containing levofloxacin are needed.

Current Worldwide Trends in Pediatric Helicobacter pylori Antimicrobial Resistance.

Helicobacter pylori (H. pylori) has acquired several resistance mechanisms in order to escape the currently used eradication regimens such as mutations that impair the replication, recombination, and transcription of DNA; the antibiotics capability to interact with protein synthesis and ribosomal activity; the adequate redox state of bacterial cells; or the penicillin-binding proteins. The aim of this review was to identify the differences in pediatric H. pylori antimicrobial-resistance trends between continents and countries of the same continent. In Asian pediatric patients, the greatest antimicrobial resistance was found to metronidazole (>50%), probably due to its wide use for parasitic infections. Aside from the increased resistance to metronidazole, the reports from different Asian countries indicated also high resistance rates to clarithromycin, suggesting that ciprofloxacin-based eradication therapy and bismuth-based quadruple therapy might be optimal choices for the eradication of H. pylori in Asian pediatric population. The scarce evidence for America revealed that H. pylori strains display an increased resistance to clarithromycin (up to 79.6%), but not all studies agreed on this statement. Pediatric patients from Africa also presented the greatest resistance rate to metronidazole (91%), but the results in terms of amoxicillin remain contradictory. Nevertheless, the lowest resistance rates in most of the African studies were found for quinolones. Among European children, the most frequent antimicrobial resistance was also noticed for metronidazole and clarithromycin (up to 59% and 45%) but with a predominance for clarithromycin as compared to other continents. The differences in antibiotic use among continents and countries worldwide is clearly responsible for the discrepancies regarding H. pylori antimicrobial-resistance patterns, emphasizing the crucial role of global judicious antibiotic use in order to control the increasing resistance rates worldwide.

Second-line levofloxacin-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori eradication and long-term changes to the gut microbiota and antibiotic resistome: a multicentre, open-label, randomised controlled trial

Levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication after failure of clarithromycin-based therapy. However, resistance to levofloxacin has increased in the past decade. Furthermore, little is known about the long-term effects of H pylori eradication on the antibiotic resistome. In this study, we compared these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters. We did a multicentre, open-label, parallel group, randomised controlled trial at eight hospitals in Taiwan. Adult patients (age ≥20 years) with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days (EAML14; esomeprazole 40 mg and amoxicillin 1 g for 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for 7 days, all twice-daily) or bismuth-based quadruple therapy for 10 days (BQ10; esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). All investigators were masked to the randomisation sequence. The primary endpoint was H pylori eradication rate measured by 13C urea breath test 6 weeks after second-line treatment according to both intention-to-treat (ITT) and per-protocol analysis. The microbiota composition and antibiotic resistome of faecal samples collected at baseline (before treatment) and at 2 weeks, 8 weeks, and 1 year after eradication therapy was profiled by shotgun metagenomic sequencing and 16S rRNA gene sequencing. The frequency of adverse effects and changes in the gut microbiota and antibiotic resistome were assessed in all participants with available data. The trial is complete and registered with ClinicalTrails.gov, NCT03148366. Between Feb 25, 2015, and Dec 11, 2020, 560 patients were randomly assigned to receive EAML14 or BQ10 (n=280 per group; 261 [47%] men and 299 [53%] women). Mean age was 55·9 years (SD 12·7) in the EAML14 group and 54·9 years (12·3) in the BQ10 group. Eradication of H pylori was achieved in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group according to ITT analysis (risk difference -0·4%, 95% CI -5·8 to 5·1; p=0·90). In the per-protocol analysis, 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group achieved H pylori eradication (risk difference 2·7%, 95% CI -0·2 to 7·4; p=0·27). Transient perturbation of faecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10. Diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies. On shotgun sequencing, we observed significant increases in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10-10) at week 2, which were restored to pretreatment level by week 8. The resistance rates of Escherichia coli and Klebsiella pneumonia to levofloxacin, ciprofloxacin, ampicillin (ampicillin-sulbactam for K pneumonia), and various cephalosporins were significantly increased in the EAML14 group compared with in the BQ10 group at week 2, which were restored to pretreatment levels and showed no significant differences at week 8 and 1 year. The frequency of any adverse effects was significantly higher after BQ10 therapy (211 [77%] of 273 participants) than after EAML14 therapy (134 [48%] of 277; p<0·0001). We found no evidence of superiority between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The transient increase in the antibiotic resistome and perturbation of faecal microbiota diversity were largely restored to pretreatment state from 2 months to 1 year after eradication therapy. The Ministry of Science and Technology of Taiwan, the Ministry of Health and Welfare of Taiwan, National Taiwan University Hospital, Taipei Veteran General Hospital, and the Australian Federal Government through the St George and Sutherland Medical Research Foundation. For the Chinese translation of the abstract see Supplementary Materials section.

A Comparison of Doxycycline and Amoxicillin Containing Quadruple Eradication Therapy for Treating Helicobacter pylori-Infected Duodenal Ulcers: A Multicenter, Opened, Randomized Controlled Trial in China.

Background: Increased antibiotic resistance is one of the major factors contributing to the failure of H. pylori eradication. This study aimed to compare the efficacy and safety of doxycycline and amoxicillin, both critical components for bismuth-based quadruple therapy, for the first-line treatment of H. pylori-infected duodenal ulcers. Methods: An open, randomized case-controlled, multicenter trial was conducted in seven hospitals in China. A total of 184 eligible participants were divided into an IDFB (ilaprazole 5 mg, doxycycline 100 mg, furazolidone 100 mg, and bismuth 220 mg bid) or IAFB (ilaprazole 5 mg, amoxicillin 1000 mg, furazolidone 100 mg, and bismuth 220 mg bid) group for 14 days. Both groups were administrated with ilaprazole 5 mg qd for another 14 days. The main outcome was an H. pylori eradication rate; secondary outcomes were ulcer healing, relief of symptoms, and incidence of adverse effects. Results: The H. pylori eradication rates were 85.9% (95% CI 78.6−93.9) in the IDFB vs. 84.8% (95% CI 77.3−92.3) in the IAFB group in ITT analysis (p > 0.05), and 92.9% (95% CI 87.4−98.5) vs. and 91.8% (95% CI 85.8−97.7) in PP analysis (p > 0.05). The overall ulcer healing rates of IDFB and IAFB were 79.1% and 84.7% (p > 0.05), both effective in relieving symptoms. Only nine participants had adverse reactions in this trial (4/92 in IDFB and 5/92 in IAFB). Conclusion: A bismuth quadruple regimen containing doxycycline or amoxicillin could be an effective and safe treatment for H. pylori eradication, while doxycycline replacement is an alternative for participants with penicillin allergy.

S3745 An Uncommon Case of Helicobacter pylori-Negative Gastric MALT Lymphoma

Introduction: Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is a type of non-Hodgkin's lymphoma with concomitant H. pylori infection. Approximately 5-10% of patients are not. Recent studies on H. pylori-negative gastric MALT lymphomas have suggested that H. pylori eradication therapy is effective in a proportion of patients with this disease and could even be considered a first-line treatment. Here, we present this uncommon and unique case. Case Description/Methods: A 58-year-old man, with PMH of prostate cancer and DVT not on anticoagulation, was initially admitted for seizures and altered mental status under the impression of bacterial meningitis. He had an upper GI bleed during the same hospitalization, and an inpatient upper endoscopy showed a Forrest 1a ulcer in the gastric fundus s/p clipping (Fig 1A). A repeat upper endoscopy three months later showed gastric erythema and a 6 mm non-bleeding healing gastric ulcer in the fundus (Fig 1B). The pathology report of antrum biopsy showed fundic and transitional zone gastric mucosa, mild chronic gastritis without intestinal metaplasia or dysplasia, and the presence of a few atypical lymphocytes. The body biopsy showed fundic/body type gastric mucosa, and findings were compatible with low-grade B-cell lymphoma, favoring extranodal marginal zone lymphoma of MALT lymphoma (Fig 1C). The patient was empirically treated for H. pylori with Bismuth-based quadruple therapy. The patient improved on follow-up with GI. Hematology-Oncology is currently planning for FISH for t(11;18) and/or MYD88 mutation status to assist in the differential, as the H. pylori strain was negative on biopsy. Discussion: Several theories describe pathways for lymphoid proliferation in H. pylori-negative patients, but the exact mechanism has yet to be determined. Currently, it is deemed multifactorial. There is a high incidence of translocation (11;18)(q21;q21) in H. pylori-negative MALT lymphomas is seen. Using radiation therapy for patients with early-stage (Lugano I/II) gastric MALT lymphomas that are negative for H. pylori infection is recommended, with clinical remission rates of up to 100%. Conversely, organ-preserving therapy has no added benefit and surgical treatment is rarely pursued. Therefore, it is recommended to eliminate the presence of H. pylori and evaluate for this translocation. Recent studies have suggested that H. pylori eradication therapy is effective in some proportion of these patients and could be considered a first-line treatment.Figure 1.: A) Upper endoscopy image of Forrest Class 1a ulcer s/p two clips. There is a spurting gastric ulcer with spurting hemorrhage. B) Upper endoscopy of gastric erythema and a 6 mm non-bleeding healing gastric ulcer in the fundus. C) Pathology: Low power view, H&E stain, of antrum biopsy showing fundic and transitional zone gastric mucosa, mild chronic gastritis without intestinal metaplasia or dysplasia, and the presence of a few atypical lymphocytes Immunohistochemistry studies showed atypical lymphocytes CD20+, CD79a+, PAX5+, CD5-, CD10-, BCL6-, BCL2+, CD43+, CyclinD1-, BCL6, and CD10, highlighting very small, scattered, disrupted germinal centers. CD3 and CD5 highlighted numerous admixed T-cells. Ki-67 was overall low (5-10%). Kappa(ish) and Lambda(ish) stains showed that the plasma cells were kappa-restricted, and had low mitotic activity, supporting the diagnosis of marginal zone lymphoma.

Single-capsule bismuth-based quadruple therapy as a rescue therapy for Helicobacter pylori eradication

Introduction Helicobacter pylori (H. pylori) infection is highly prevalent in Portugal and its eradication is formally recommended. However, the indiscriminate use of antimicrobials has led to a drastic rise in antibiotic resistance, with the failure of traditional eradication schemes. A single-capsule bismuth-based quadruple therapy became recently available in Portugal. This study aims to evaluate the efficacy and safety of a bismuth-based quadruple therapy as a second-line or rescue therapy. Patients and methods This was a multicentric study. All consecutive patients that were treated with bismuth-based quadruple therapy, as second-line or salvage treatment between July 2017 and April 2019 were enrolled. Their medical records were reviewed and clinical and laboratorial parameters, as well as data on treatment efficacy and adverse events were retrieved. Patients were also contacted by phone after treatment to confirm compliance, adverse events, and global satisfaction with this specific therapy. Results A total of 151 subjects were included (female—68.9%; mean age—56 ± 13.5 years). Patients were previously submitted to 212 eradication schemes (Median-1; 1–5; IQR:4): 33.5% triple clarithromycin-based, 25% sequential, 7.5% concomitant, 5.2% others, and in 28.8% it was not possible to know the previous eradication scheme(s) followed by the patient. The PPI of choice was esomeprazole (39.7%), followed by omeprazole (27.8%). Compliance was achieved in 93.4% and the overall eradication rate was 90.1% (95% CI: 84.6–94.2). Treatment-related adverse effects were experienced by 63 patients (41.7%; 95% CI: 34–49.7), being mild in 29, moderate in 19, and severe in 15. The main drawbacks of the treatment, from the patient’s perspective, were the high price (47%) and the adverse effects (16.6%). Failure to eradicate H. pylori was correlated with the following: previous rifabutin-based scheme (0 vs. 100%; p = 0.010) and a higher number of previous treatment schemes (1.5 ± 0.7 vs. 2.3 ± 1.2; p < 0.001). Conclusion In this South-European country a single-capsule bismuth-based quadruple therapy is an excellent option as a second-line or rescue therapy, with acceptable compliance and side effects.

Effective Eradication Regimen and Duration According to the Clarithromycin Susceptibility of Helicobacter pylori Determined Using Dual Priming Oligonucleotide-Based Multiplex Polymerase Chain Reaction.

Dual priming oligonucleotide-based multiplex polymerase chain reaction (DPO-PCR) has recently been used for both the detection of Helicobacter pylori and the identification of H. pylori 23S ribosomal RNA point mutations that cause clarithromycin resistance. The aim of this study was to investigate the duration of effective standard triple therapy in a clarithromycin susceptible group and of bismuth-based quadruple therapy in a resistant group based on DPO-PCR. We retrospectively analyzed the electronic medical records of 184 patients who, between September 2019 and December 2020, received eradication therapy following detection of H. pylori, and the subsequent identification of the clarithromycin susceptibility of their H. pylori using DPO-PCR. Patients were treated with 7- or 14-day standard triple therapy in the clarithromycin susceptible group, whereas 7- or 14-day bismuth-based quadruple therapy in the clarithromycin resistance group. In the clarithromycin susceptible group, per-protocol analyses showed eradication rates of 87.5% (42/48; 95% confidence interval [CI], 77.1% to 95.8%) for 7-day therapy and 87.2% (41/47; 95% CI, 78.7% to 95.7%) for 14-day therapy (p=0.969). The eradication rates in the clarithromycin resistance group were 91.4% (32/35; 95% CI, 80.0% to 100.0%) for 7-day therapy and 90.3% (28/31; 95% CI, 77.4% to 100.0%) for 14-day therapy (p=0.876). There was no significant difference in the eradication rates, patient compliance, or rate of adverse events between the 7- and 14-day therapies for both groups. Compared to the 14-day therapy, 7-day eradication therapy is sufficient after DPO-PCR-based clarithromycin susceptibility testing.

Efficacy of Bismuth-based Quadruple Therapy as First-line Treatment for Clarithromycin-resistant Helicobacter pylori Infection

Efficacy of Bismuth-based Quadruple Therapy as First-line Treatment for Clarithromycin-resistant Helicobacter pylori Infection

Clinical Characteristics and Treatment Pathway of Patients Treated with Helicobacter pylori Infection-A Single Center Cohort Study Using Common Data Model

Background/Aims: Changing trends in the &lt;i&gt;Helicobacter pylori&lt;/i&gt; (&lt;i&gt;H. pylori&lt;/i&gt;) eradication protocol have not been investigated after the publication of the third-revised Korean guideline in 2013. We aimed to analyze the clinical characteristics of &lt;i&gt;H. pylori&lt;/i&gt;-infected patients alongside their treatment protocols using a common data model (CDM).Materials and Methods: A 16-year electronic health record (of 1,689,604 patients from 2004 to 2019) was converted into a CDM in Kangdong Sacred Heart Hospital. We extracted records of patients who underwent the rapid urease test or serum anti-&lt;i&gt;H. pylori&lt;/i&gt; IgG assay. The treatment protocols were visualized using a sunburst plot. We investigated the clinical characteristics and medication history of patients who underwent a urea breath test after clarithromycin-based eradication therapy.Results: Out of 29,458 patients tested for &lt;i&gt;H. pylori&lt;/i&gt; infection, 7,647 received a treatment protocol. Among them, 72.5% received a 7~14 days protocol comprising a proton pump inhibitor (PPI), amoxicillin, and clarithromycin. The proportion of patients treated with the first-line protocol (PPI, bismuth, tetracycline, and metronidazole) slightly increased from 1.9% (before 2014) to 3.3% (after 2014) (P&lt;0.001). The percentages of patients with of previous exposure to macrolides (14.7% vs. 5.5%, P&lt;0.001) or amoxicillin (10.6% vs. 7.3%, P=0.006) were higher in patients with previous clarithromycin-based eradication failure.Conclusions: The &lt;i&gt;H. pylori&lt;/i&gt; treatment protocol was not significantly modified despite the updates in the clinical guideline. There was only 1.4 percentage point increase in bismuth-based quadruple therapy as first-line eradication therapy even after the announcement of revised Korean guideline in 2013.